A correlation method was developed to examine functional interactions between brain regions by correlating regional cerebral metabolic rates for glucose as determined by positron emission tomography in humans. The method was applied to regional metabolic data obtained by positron emission tomography (PET) from 14 young adult patients with Down Syndrome and 24 matched control subjects. Compared with controls, the Down Syndrome group had lower values for many correlations within and between the frontal and parietal lobes (including Broca' s speech area), indicating a disruption of neural systems associated with language and with attention in Down Syndrome. The correlation matrix method was applied to analyze glucose metabolic rates in awake Fischer-344 rats. Correlations between rCMRglc in cho- linergic nuclei and frontoparietal cortex increased in rats 2 weeks after ibotenic acid lesions of the cholinergic nucleus basalis magnocellularis, indicating altered functional interactions between the remaining cholinergic nuclei and cortex. The correlation method was applied to rCBF data obtained in humans with PET during two visual processing tasks: face matching and dot location following rotation. Correlations among appropriate poster 1 or brain regions were significantly large on the right side of the brain, but not on the left, although rCBF was bilaterally increased during the tasks, suggesting that these tasks are performed to a greater degree by the right posterior hemisphere than by the left. A computer simulation model was developed to partially validate the correlational analysis as applied to metabolic data, demonstrating that correlational analysis yields information on regional involvement in neural systems not evident in the pattern of absolute metabolic